Genetic Polymorphism and Disease

Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Foreword
Foreword
Preface
Acknowledgments
Editors
Contributors
1. Genetic Polymorphisms – Classification, Structure, Detection and Function
1.1 Introduction
1.2 Genetic Polymorphisms
1.2.1 Types of Genetic Polymorphisms
1.2.1.1 Single Nucleotide Polymorphisms (SNPs)
1.2.1.2 Copy Number Variations (CNVs)
1.2.1.3 Copy Neutral Variations
1.2.1.4 Small Indel (Insertion and Deletion) Polymorphisms
1.2.1.5 Genomic or DNA Repetitive Sequences and Repetitive Sequence Polymorphisms
1.3 Conclusions
Abbreviations
References
2. Clinical Relevance of Pharmacogenomics – a Road to Personalized Medicine
2.1 Introduction
2.1.1 Definition and Historical Perspective of Pharmacogenomics
2.2 Influence of Pharmacogenomics on Pharmacokinetics and Pharmacodynamics
2.2.1 Role of Pharmacogenomics in Phase I Drug-Metabolizing Enzymes
2.2.2 Role of Pharmacogenomics in Phase II Drug-Metabolizing Enzymes
2.2.3 Role of Pharmacogenomics on Drug Transporters and Drug Targets
2.3 Applications of Pharmacogenomics in Therapeutics
2.3.1 Pharmacogenomics in Cancer Therapy
2.3.2 Pharmacogenomics in Neurological Disorders
2.3.3 Pharmacogenomics in Respiratory Disorders
2.3.4 Pharmacogenomics in Diabetes Mellitus
2.3.5 Pharmacogenomics in Cardiovascular Disorders
2.3.6 Pharmacogenomics in Pain
2.4 Conclusions and Future Perspectives
Abbreviations
References
3. Diabetes and Role of SNPs in Diabetes Susceptibility
3.1 Introduction
3.2 Types
3.2.1 Risk Factors
3.3 Classification and Challenges
3.3.1 Type 1 Diabetes Mellitus
3.3.1.1 Autoimmune Type 1 Diabetes
3.3.1.2 Idiopathic Type 1 Diabetes
3.3.2 Type 2 Diabetes Mellitus
3.3.3 Gestational Diabetes Mellitus (GDM)
3.3.4 Other Specific Types
3.3.4.1 Monogenic Diabetes
3.3.4.2 Mitochondrial Diabetes
3.3.4.3 Diabetes of Exocrine Pancreas
3.4 Genetic Background
3.4.1 ß-Cell Dysfunction Pathway
3.4.2 TXNIP (Thioredoxin-Interacting Protein) in Pancreatic ß-Cell Dysfunction
3.4.3 Insulin Signaling Pathway in Diabetes
3.5 Polymorphisms and Susceptibility to Diabetes Disease
3.5.1 T1D
3.5.1.1 SNPs in Diabetes Type 1
3.5.2 Type 2 Diabetes
3.5.2.1 TCF7L2
3.5.2.2 IGF2BP2
3.5.2.3 CDKAL1
3.5.2.4 FTO
3.5.2.5 SLC30A8
3.5.2.6 KCNJ11
3.5.2.7 PPARG
3.5.2.8 CDKN2A
3.5.2.9 HHEX
3.5.2.10 SREBF1
3.5.3 Gestational Diabetes Mellitus (GDM)
3.5.3.1 WFS1
3.5.3.2 MTNR1B
3.6 Conclusions
Abbreviations
References
4. Genetic Polymorphisms Associated with Innate Immune Response to Malaria
4.1 Introduction to the Biology of Gene Polymorphism
4.1.1 Malaria
4.1.2 Human Leukocyte Antigen (HLA) and Malaria
4.2 Structure and Function of Immunoglobulins
4.2.1 Immunoglobulins and Malaria Protection
4.3 Immunoglobulins and Fc Receptors
4.3.1 The Fc.R Family
4.3.2 Fcγ RIIa-R/ H131 Genotypes and Malaria Infection
4.3.3 Fcγ RIIIa-F/ V176 Genotypes and Malaria Infection
4.3.4 Fcγ RIIIb-NA1/ NA2 Genotypes and Malaria Infection
4.4 Toll-Like Receptors' Polymorphisms, Malaria Susceptibility and Pathogenesis
4.5 Tumor Necrosis Factor (TNF)
4.6 Nitric Oxide (NO)
4.7 Heme Oxygenase
4.8 Conclusions
Abbreviations
References
5. Xenobiotic Metabolic Enzyme Polymorphisms and Cancer Susceptibility
5.1 Introduction
5.2 Glutathione S-Transferases (GSTs)
5.2.1 Polymorphism of GSTs and Cancers
5.2.1.1 GSTs and Head-and-Neck Carcinoma
5.2.1.2 GSTs and Breast Cancer
5.2.1.3 GSTs and Lung Cancer
5.2.1.4 GSTs and Esophageal Cancer
5.2.1.5 GSTS and Gastric Cancer
5.2.1.6 GSTs and Colorectal Cancer
5.2.1.7 GSTS and Hepatocellular Carcinoma
5.2.1.8 GSTs and Prostate Cancer
5.2.2 Conclusions
5.3 Arylamine N-Acetyltransferases (NATs)
5.3.1 Polymorphism of NATs and Cancers
5.3.1.1 NATs and Head-and-Neck Cancer
5.3.1.2 NATs and Breast Cancer
5.3.1.3 NATs and Lung Cancer
5.3.1.4 NATs and Esophageal Cancer
5.3.1.5 NATs and Gastric Cancer
5.3.1.6 NATs and Colorectal Cancer
5.3.1.7 NATs and Prostate Cancer
5.3.2 Conclusions
5.4 Cytochrome P450 (CYP)
5.4.1 Polymorphism of CYPs and Cancers
5.4.1.1 CYPs and Head-and-Neck Cancer
5.4.1.2 CYPs and Breast Cancer
5.4.1.3 CYPs and Lung Cancer
5.4.1.4 CYPs and Esophageal Cancer
5.4.1.5 CYPs and CRC
5.4.1.6 CYPs and Prostate Cancer
5.4.2 Conclusions
Abbreviations
References
6. Genetic Polymorphisms in Matrix Metalloproteinase (MMP) Genes and Cancer
6.1 Introduction
6.2 Structural Aspects of Matrix Metalloproteinases
6.3 Classification of Matrix Metalloproteinases
6.4 Regulation of Matrix Metalloproteinases
6.4.1 Transcriptional and Post-Transcriptional Regulation of Gene Expression
6.4.2 Inhibition of Matrix Metalloproteinases by Specific and Non-Specific Inhibitors
6.4.3 Tissue Inhibitors of Metalloproteinases (TIMPs)
6.5 Role of Matrix Metalloproteinases and Polymorphisms in Matrix Metalloproteinase Genes in Cancer
6.5.1 Polymorphisms in Matrix Metalloproteinase7 (MMP7) Gene
6.5.2 Polymorphisms in Matrix Metalloproteinase1 (MMP1) Gene
6.5.3 Polymorphisms in Matrix Metalloproteinase8 (MMP8) Gene
6.5.4 Polymorphisms in Matrix Metalloproteinase13 (MMP13) Gene
6.5.5 Polymorphisms in Matrix Metalloproteinase3 (MMP3) Gene
6.5.6 Polymorphisms in Matrix Metalloproteinase2 (MMP2) Gene
6.5.7 Polymorphisms in Matrix Metalloproteinase 9 (MMP9) Gene
6.6 Conclusions
Abbreviations
References
7. Vitamin D Receptor Polymorphisms and Diseases
7.1 Introduction
7.1.1 Vitamin D Production and Metabolism
7.2 Vitamin D Receptor (VDR)
7.2.1 Vitamin D Signaling
7.3 VDR Polymorphisms
7.3.1 rs11568820 (CDX2)
7.3.2 rs4516035 (EcoRV)
7.3.3 rs2228570 (FokI)
7.3.4 rs757343 (Tru9I)
7.3.5 rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI)
7.4 VDR SNPs and Diseases
7.4.1 Cardiovascular Diseases
7.4.1.1 Hypertension
7.4.1.2 Diabetes Mellitus
7.4.2 Renal Diseases
7.4.3 Allergic Diseases
7.4.4 Autoimmune Diseases
7.4.5 Neurological Diseases
7.4.6 Hepatic Diseases
7.5 Conclusions
Abbreviations
References
8. Genetic Polymorphisms in Fatty Acid Metabolism Genes and Cancer Susceptibility
8.1 Introduction
8.2 Fatty Acid Metabolism
8.2.1 Fatty Acid Catabolism
8.2.2 Beta-Oxidation
8.3 Fatty Acid Metabolism Genes
8.4 Fatty Acid Metabolism and Cancer
8.5 Genetic Polymorphisms in Fatty Acid Metabolism Genes and Cancer
8.5.1 FASN Gene
8.5.1.1 Structure and Function
8.5.1.2 Reported SNPs in FASN Gene
8.5.1.3 FASN Gene Polymorphisms and Cancer
8.5.2 PPARG Gene
8.5.2.1 Structure and Function of PPARG
8.5.2.2 Reported SNPs in PPARG
8.5.2.3 PPARG Gene Polymorphisms in Cancer
8.5.3 FABPI Gene
8.5.3.1 Structure and Function
8.5.3.2 Reported SNPs in FABP1 Gene
8.5.3.3 FABP1 Gene Polymorphisms in Cancer
8.5.4 CYP2E1 Gene
8.5.4.1 Structure and Function
8.5.4.2 Reported SNPs in CYP2E1
8.5.4.3 CYP2E1 Gene Polymorphisms in Cancer
8.5.5 LIPC Gene
8.5.5.1 Structure and Function
8.5.5.2 Reported SNPs in LIPC Gene
8.5.5.3 LIPC Gene Polymorphisms in Cancer
8.6 Conclusions
Abbreviations
References
9. Single Nucleotide Polymorphisms and Parkinson's Disease Susceptibility
9.1 Introduction
9.2 Risk Factors
9.2.1 Environmental Risk Modifiers of Parkinson's Disease
9.2.1.1 Pesticides
9.2.1.2 Cigarette Smoking
9.2.1.3 Beverages
9.2.1.4 Urate
9.2.1.5 Head Injury
9.2.1.6 Drugs
9.2.1.7 Metabolic Risk Factors
9.2.2 Genetic Risk Modifiers (Contributors) of Parkinson's Disease
9.3 Genetic Polymorphisms in Parkinson's Disease
9.3.1 Gene Polymorphisms Involved in Dopamine Metabolism
9.3.2 Gene Polymorphisms Involved in Detoxification Metabolism
9.3.3 Polymorphisms of Genes Involved in Inflammatory Processes
9.3.4 Gene Polymorphisms Involved in Oxidative Stress
9.3.5 Gene Polymorphisms in Mitochondrial Function Pathway
9.3.6 Gene Polymorphisms of Trophic Factors
9.3.7 Other Gene Polymorphisms (Polymorphisms in Genes with Putative Relation)
9.4 Conclusions
Abbreviations
References
10. Genetic Polymorphisms, Role in Drug Metabolism and Effect on Clinical Pharmacy
10.1 Introduction
10.2 Genetic Polymorphisms in Drug-Metabolizing Genes
10.2.1 Poor Metabolizers
10.2.2 Intermediate Metabolizers
10.2.3 Extensive Metabolizers
10.2.4 Ultra-rapid Metabolizers
10.2.5 Normal Metabolizers
10.3 Inducers and Inhibitors
10.3.1 Extensive Metabolizer-Inhibitors
10.3.2 Poor Metabolizer-Inhibitors
10.3.3 Extensive Metabolizer-Inducers
10.3.4 Poor Metabolizer-Inducers
10.4 Genetic Variability Associated with the Phase I Enzymes
10.4.1 CYP2D6 (CYP 450 Family 2, Subfamily D, Polypeptide 6)
10.4.2 CYP2C19 (CYP 450 Family 2, Subfamily C, Polypeptide 19)
10.4.3 CYP2C9 (CYP 450 Family 2, Subfamily C, Polypeptide 9)
10.4.4 CYP3A4 (CYP 450 Family 3, Subfamily A, Polypeptide 4)
10.4.5 CYP3A5 (CYP 450 Family 3, Subfamily A, Polypeptide 5)
10.4.6 CYP3A7 (CYP 450 Family 3, Subfamily A, Polypeptide 7)
10.4.7 Other P450 Enzymes
10.4.8 Dihydropyrimidine Dehydrogenase
10.5 Genetic Variability Associated with the Phase II Enzymes
10.5.1 N-Acetyltransferase
10.5.2 Thiopurine S-Methyltransferase (TPMT)
10.5.3 UDP-glucuronosyltransferases (UGTs)
10.6 Clinical Implications of Other Drug Target Polymorphisms
10.7 Conclusions and Future Aspects
Abbreviations
References
11. Role of Genetic Polymorphisms in Chronic Inflammatory Diseases
11.1 Introduction
11.2 Inflammatory Bowel Disease (IBD)
11.2.1 Single Nucleotide Polymorphisms in IBD
11.2.1.1 Human Leukocyte Antigen (HLA) Genes and IBD
11.2.1.2 Non-Human Leukocyte Antigen (HLA) Susceptibility Genes
11.3 Rheumatoid Arthritis (RA)
11.3.1 Single Nucleotide Polymorphisms in RA
11.3.1.1 Human Leukocyte Antigen (HLA) Susceptibility Genes
11.3.1.2 Non-Human Leukocyte Antigen (HLA) Genes
11.4 Multiple Sclerosis (MS)
11.4.1 Single Nucleotide Gene Polymorphisms and MS
11.4.1.1 Human Leukocyte Antigen (HLA) Genes
11.4.1.2 Non-Human Leukocyte Antigen (HLA) Genes
11.5 Type 1 Diabetes (T1D)
11.5.1 Single Nucleotide Gene Polymorphisms and T1D
11.5.1.1 Human Leukocyte Antigen (HLA) Susceptibility Genes
11.5.1.2 Non-Human Leukocyte Antigen (HLA) Susceptibility Genes
11.6 Conclusions
Abbreviations
References
12. Single Nucleotide Polymorphism-Related Computational Resources Part I: Databases
12.1 Introduction
12.2 SNP Resources
12.2.1 The Cancer Genome Atlas (TCGA)
12.2.2 The International Cancer Genome Consortium (ICGC)
12.2.3 Single Nucleotide Polymorphism Database (dbSNP)
12.2.4 Database of Genotype and Phenotype (dbGaP)
12.2.5 1000 Genomes Project
12.2.6 Ensembl
12.2.7 ClinVar
12.2.8 dbVar and DGVa – Both for Genomic Structural Variation (GSV)
12.2.9 Database of Genomic Variants (DGV)
12.2.10 3-Dimensional Single Nucleotide Polymorphism (3DSNP)
12.2.11 RegulomeDB
12.2.12 MR-Base
12.2.13 atSNP Search
12.2.14 OncoBase
12.2.15 Catalog of Somatic Mutations in Cancer (COSMIC)
12.2.16 SNP2APA
12.2.17 Human Metabolome Database (HMDB)
12.2.18 Human Mutation Analysis (HUMA)
12.2.19 miRdSNP
12.2.20 Protein ANalysis THrough Evolutionary Relationships (PANTHER)
12.2.21 Patrocles
12.2.22 SNPeffect
12.2.23 The Total Integrated Archive of Short-Read and Array (TIARA) Database
12.2.24 Genome Variation Map (GVM)
12.2.25 Variation Annotation Database for Human (VARAdb)
12.2.26 Catalog of Human Genome-Wide Association Studies (GWAS Catalog)
12.2.27 Mouse Genome Database (MGD)
12.2.28 dbNSFP – Database of Functional Predictions and Annotations for Human Non-synonymous and Splice-Site SNVs
12.2.29 Phenome Linking to the Genome (PheLiGe)
12.2.30 GWAS Atlas
12.2.31 ncRNA-eQTL
12.2.32 HACER
12.2.33 Genomic Information Portal on Cancer Cell Lines (GENIPAC)
12.2.34 Database of Genomic Variants of Oral Cancer (dbGENVOC)
12.2.35 CancerSplicingQTL
12.2.36 SweGen
12.2.37 RMBase
12.2.38 SNP2TFBS
12.2.39 RAAR – Regulators of Androgen Action Resource
12.2.40 LincSNP 3.0
12.2.41 SomamiR
12.2.42 MSDD PMID
12.2.43 miRNASNP
12.3 Other Databases Related to SNP Research
12.4 Importance of SNP Data Resources in Research
12.5 Conclusions and Way Forward
Abbreviations
References
13. Single Nucleotide Polymorphism-Related Computational Resources Part II: Algorithms
13.1 Introduction
13.2 Bioinformatics Approaches Used in Predicting SNPs
13.2.1 The UCSC Genome Browser
13.2.2 GW-SEM
13.2.3 TransAT
13.2.4 GADGETS
13.2.5 snpXplorer
13.2.6 EpiGEN
13.2.7 HiGwas
13.2.8 SEMpl
13.2.9 SnpHub
13.2.10 GeDi
13.2.11 CKAT
13.2.12 ICGRM
13.2.13 CoMutPlotter
13.2.14 CERENKOV
13.2.15 gpart
13.2.16 CASMAP
13.2.17 LD-annot
13.2.18 Multi-SNP Mediation Intersection-Union Test
13.2.19 Varanto
13.2.20 graph-GPA
13.2.21 SNPDelScore
13.2.22 snpEnrichR
13.2.23 WISH-R
13.2.24 FATHMM-XF (FATHMM with an eXtended Feature Set)
13.2.25 BSviewer
13.2.26 Lep-MAP3
13.2.27 SCcaller
13.2.28 TSGSIS
13.2.29 Heap
13.2.30 DnaSP
13.2.31 HAPRAP
13.2.32 CollapsABEL
13.2.33 Monovar
13.2.34 NASP
13.2.35 PredictSNP2
13.2.36 4Pipe4
13.2.37 ALICE
13.2.38 Altools
13.2.39 BAM-matcher
13.2.40 SNP-sites
13.2.41 Ensembl Variant Effect Predictor (VEP)
13.2.42 LAMPLINK
13.2.43 CINOEDV
13.2.44 JEPEGMIX
13.2.45 snpGeneSets
13.2.46 traseR
13.2.47 SNPStats
13.2.48 SNPsnap
13.2.49 Phyre2
13.2.50 LDlink
13.2.51 PROVEAN
13.2.52 SNP2GO
13.2.53 SNPsea
13.2.54 PolyPhen-2
13.2.55 GWIS
13.2.56 AnnTools
13.2.57 SIFT
13.2.58 GCTA
13.2.59 adegenet
13.2.60 SNPinfo
13.2.61 SNAP
13.2.62 WASP
13.2.63 PhD-SNP
13.2.64 novoSNP
13.2.65 PolyBayes
13.2.66 PolyPhred
13.2.67 BGT
13.3 Conclusions
Abbreviations
References
14. Role of Single Nucleotide Polymorphisms (SNPs) in Common Migraine
14.1 Introduction
14.2 Migraine
14.3 Types of Migraine
14.3.1 Migraine without Aura (MO)
14.3.2 Migraine with Aura (MA)
14.4 Role of SNPs in Migraine
14.4.1 Neurological Genes
14.4.2 Neurotransmission Genes
14.4.3 Vascular Genes
14.4.4 Neurotrophic Genes
14.4.5 Hormonal Genes
14.4.6 Inflammatory Genes
14.5 Important Gene SNPs in Migraine
14.5.1 PRDM
14.5.2 TRPM8
14.5.3 MTDH
14.5.4 MEF2D
14.5.5 MMP16
14.5.6 LRP1
14.5.7 MTHFR
14.5.8 BDNF & NGF
14.5.9 TNF
14.5.10 ESRs
14.6 Conclusions
Abbreviations
References
15. The Role of Vitamin D Single Nucleotide Polymorphisms in Cancer Susceptibility
15.1 Introduction
15.1.1 Transport of Vitamin D
15.1.2 Analogs of Vitamin D
15.1.3 Vitamin D Receptors
15.1.3.1 Nuclear VDR
15.1.3.2 Membrane VDR
15.2 Vitamin D Signaling Pathways
15.3 Genomic and Non-genomic Implications of Vitamin D
15.4 Role of Vitamin D and Its SNPs in Health and Diseases
15.5 The Role of Vitamin D in Cancer
15.5.1 Vitamin D and Cancer
15.5.2 VDR Polymorphisms and Cancer
15.5.3 Role of Vitamin D and Its Receptors in All Cancer Types
15.5.3.1 Gynecological Malignancy
15.5.3.2 Hematological Cancer
15.5.3.3 Urinary Tract Cancer
15.5.3.4 Pediatric Tumors
15.5.3.5 Prostate Cancer
15.5.3.6 Melanoma
15.5.3.7 Gastric Cancer
15.5.3.8 Other Types of Malignancies
15.6 Strength and Limitations of the Evidence of Vitamin D Role in Cancer Susceptibility
15.7 Potential of Vitamin D and Its Receptors in Cancer Therapy
15.7.1 Vitamin D and Proliferation
15.7.2 Vitamin D and Metastasis
15.7.3 Vitamin D and Angiogenesis
15.8 Future Implications
15.9 Conclusions
Abbreviations
References
16. Role of Genetic Polymorphisms in Lipid Metabolism Pathways in Modulating Cancer Promotion
16.1 Introduction
16.2 De novo Lipid Synthesis
16.3 ACSL
16.3.1 ACSL5
16.4 PPARG
16.5 Lipoprotein Lipase and Hepatic Lipase
16.5.1 LPL and LIPC SNPs
16.6 ApoE
16.7 Polyunsaturated Fatty Acids Metabolism
16.8 CYP
16.8.1 CYP1A2
16.9 Prostaglandin-Endoperoxide Synthases (PTGS)
16.10 Conclusions
Abbreviations
References
17. Toll-Like Receptor (TLR) Polymorphisms in Prostate Cancer
17.1 Introduction
17.2 Urogenital System: Prostate Anatomy, Structure and Characteristics
17.3 Prostate Cancer
17.4 Classification and Grading of Prostate Cancer
17.5 Epidemiology of Prostate Cancer
17.6 Prostate Cancer Risk Factors
17.7 Single Nucleotide Polymorphisms and Cancers
17.8 Introduction to Toll-Like Receptors, Structures, Locations and Functions in Normal Health
17.8.1 Toll-Like Receptors, Cascade of TLR Signaling Pathways and the Related Adaptors
17.8.2 Toll-Like Receptors and Tumor Biology
17.9 Immunogenetics and Toll-Like Receptors
17.10 Toll-Like Receptors: Single Nucleotide Polymorphisms and Cancers
17.10.1 Toll-Like Receptors, Single Nucleotide Polymorphism in Toll-Like Receptors and Prostate Cancer
17.11 Conclusions
Acknowledgments
Abbreviations
References
18. Role of Single Nucleotide Polymorphism of Cytochrome P450 Genes in Cancer Susceptibility
18.1 Introduction
18.2 Classification of CYP Enzymes
18.3 Mechanism of Working of CYP Enzymes
18.4 Expression and Functioning of CYP Enzymes
18.5 Role of Cytochrome P450 in Cancers
18.5.1 Lung Cancer
18.5.2 Breast Cancer
18.5.3 Liver cancer
18.5.4 Gastric Cancer
18.5.5 Colorectal Cancer (CRC)
18.5.6 Prostate Cancer
18.5.7 Head-and-Neck Cancer
18.6 Conclusions
Abbreviations
Bibliography
19. Role of Single Nucleotide Polymorphisms of Inflammatory Molecules in Susceptibility to Cardiovascular Diseases (CVDs)
19.1 Introduction
19.1.1 Cardiovascular Disease (CVD) and Its Types
19.1.2 Risk Factors
19.2 Cardiovascular Disease-Associated Inflammatory Pathways
19.2.1 HDL (High-Density Lipoprotein) and Apolipoprotein-Associated Inflammatory Pathway
19.2.2 Vitamin D Receptor(VDR)-Associated Inflammatory Pathway
19.2.3 Adiponectin-Associated Inflammatory Pathway
19.2.4 General Role of Inflammatory Molecules in Cardiovascular Diseases
19.2.4.1 Relation between Cardiovascular Diseases and Inflammation
19.3 Genetic Polymorphisms and Their Role in Inflammatory Molecule-Coding Gene in CVDs
19.3.1 Role of SNPs in IL-1-Coding Gene in Cardiovascular Disease
19.3.2 Role of SNPs in IL-6-Coding Gene in Cardiovascular Disease
19.3.3 Role of SNPs in IL-8-Coding Gene in Cardiovascular Disease
19.3.4 Role of SNPs in IL-10-Coding Gene in Cardiovascular Disease
19.3.5 Role of SNPs in IL-18-Coding Gene in Cardiovascular Disease
19.3.6 Role of SNPs in IL-35-Coding Gene in Cardiovascular Disease
19.3.7 Role of SNPs in IL-37-Coding Gene in Cardiovascular Disease
19.3.8 Role of SNPs in TNF-α-Coding Gene in Cardiovascular Disease
19.3.9 Role of SNPs in TGF-β-Coding Gene in Cardiovascular Disease
19.3.10 Role of SNPs in CRP (C-Reactive Protein)-Coding Gene in Cardiovascular Disease
19.4 Conclusions
Abbreviations
References
20. Role of Genetic Polymorphisms in the Etiopathogenesis of Esophageal Cancer
20.1 Introduction
20.2 Pathogenesis of Esophageal Cancer
20.3 Risk Factors for Esophageal Cancer
20.4 Genetic Background of Esophageal Cancer
20.4.1 Genes That Control Cell Division or Differentiation
20.4.2 RAS Signaling or Receptor Tyrosine Kinase (RTK) and Epidermal Growth Factor Receptor (EGFR)
20.4.3 Genetic Variations in VEGF Signaling Pathway
20.4.4 Epigenetic Factors
20.5 Genetic Polymorphisms and Esophageal Cancer
20.5.1 Genetic Polymorphisms in ESCC
20.5.1.1 Xenobiotic-Metabolizing Enzymes (XMEs)
20.5.1.2 Enzymes Involved in Repair Mechanisms, Cell Cycle Regulation, and Apoptosis
20.5.1.3 Others
20.5.2 Genetic Polymorphisms in EAC
20.6 Role of Genetic Polymorphisms in EC Prognosis
20.7 Future Perspectives
Abbreviations
References
21. Cytokine Polymorphisms and Their Role in Modulating Cancer Risk
21.1 Introduction
21.2 Classification of Cytokines
21.3 History of Cytokines
21.4 Types of Cytokines
21.5 Cytokine Signaling
21.6 Role of Cytokines in Cancer
21.7 Cytokine Polymorphisms and Cancer
21.7.1 Interleukin 1
21.7.1.1 Interleukin 1 Structure and Function
21.7.1.2 Reported SNPs in Interleukin 1
21.7.1.3 Interleukin 1 Polymorphisms in Cancer
21.7.2 Interleukin 6
21.7.2.1 Interleukin 6 Structure and Function
21.7.2.2 Reported SNPs in Interleukin 6
21.7.2.3 Interleukin 6 Polymorphisms and Cancer
21.7.3 Interleukin 4
21.7.3.1 Interleukin 4 Structure and Function
21.7.3.2 Reported SNPs in Interleukin 4
21.7.3.3 Interleukin 4 Polymorphisms and Cancer
21.7.4 Interleukin 13
21.7.4.1 Interleukin 13 Structure and Function
21.7.4.2 Reported SNPs in Interleukin 13
21.7.4.3 Interleukin 13 Polymorphisms and Cancer
21.7.5 Tumor Necrosis Factor Alpha
21.7.5.1 TNF Structure and Function
21.7.5.2 Reported SNPs in TNF
21.7.5.3 TNF Polymorphisms and Cancer
21.7.6 Interferons
21.7.6.1 Interferon Structure and Function
21.7.6.2 Reported SNPs in Interferon
21.7.6.3 Interferon Polymorphisms in Cancer
21.8 Conclusions
Abbreviations
References
22. Gastric Cancer and Genetic Polymorphisms in Modulating the Susceptibility
22.1 Introduction
22.1.1 Worldwide Scenario of Gastric Cancer Incidence and Mortality
22.1.2 Etiology of Gastric Cancer
22.2 Genetic Polymorphisms in Relation to Gastric Cancer Susceptibility
22.2.1 Genetic Variability in Metabolic Enzymes Involved in the Detoxification of Carcinogens
22.2.1.1 Cytochrome P450 Gene Polymorphism
22.2.1.2 Glutathione S-Transferase Gene Polymorphism
GSTM1 (Glutathione S-transferase Mu1)
22.2.2 Genetic Variability of Proteins Involved in Mechanisms of DNA Repair
22.2.2.1 XRCC1 (X-ray repair cross-complementing group 1)
22.2.2.2 APE1 (Apurinic/apyrimidinic endonuclease 1)
22.2.2.3 ERCC5 (Excision repair cross-complementing group 5)
22.2.3 Genetic Variability of Immunogenic Factors
TNF (Tumor necrosis factor)
22.2.4 Genetic Variations in Tumor Suppressor Genes and Apoptotic Pathway
22.2.4.1 TP53 (Tumor Protein)
22.2.5 Genetic Variations in Cell Signaling Pathways and Gastric Cancer Susceptibility
22.2.5.1 RAS (rat sarcoma virus)
22.2.5.2 ERBB2 (V-erb-b2 erythroblastic leukemia viral oncogene homolog 2)
22.2.5.3 CDH1 (Cadherin 1, type1, E-cadherin epithelial)
22.2.5.4 DNTM1 (DNA (cytosine-5)-methyltransferase 1) gene
22.3 Conclusions
Abbreviations
References
23. Cytokine Gene Polymorphisms and Their Role in Autoimmune Diseases
23.1 Introduction
23.2 History of Cytokines
23.3 Classification of Cytokines and Their Clinical Significance
23.3.1 Pro-inflammatory Cytokines
23.3.2 Anti-inflammatory Cytokines
23.4 Gene Polymorphisms in Cytokine Genes
23.4.1 Effects
23.5 Cytokine Polymorphisms and Autoimmune Diseases
23.5.1 Interleukins
23.5.2 Tumour Necrosis Factor (TNF)
23.5.3 Interferons
23.6 Conclusions
Abbreviations
References
24. Genomic Disturbances Associated with Penile Cancer and Novel Therapies
24.1 Introduction
24.2 Pathology and Pathogenesis of PeCa
24.3 Single Nucleotide Polymorphism Molecular Pathways
24.4 Chronic Inflammation and Chromosomal Imbalance
24.5 Novel Therapies
24.6 Conclusions
Abbreviations
References
25. Role of Genetic Polymorphisms in Gastric Cancer Susceptibility
25.1 Introduction
25.1.1 Risk Factors
25.1.2 Gastric Cancer Classification
25.1.3 Staging
25.2 Genetic Profile of Gastric Cancer
25.2.1 Hereditary Gastric Cancer Syndromes
25.2.2 Acquired Genetic Abnormalities in Gastric Cancer
25.2.2.1 Chromosomal Insufficiency
25.2.2.2 Microsatellite Instability
25.2.2.3 Epigenetic Changes
25.2.2.4 Single Nucleotide Polymorphisms (SNPs)
25.3 Methodologies for Studying Genetic Polymorphism in Gastric Cancer
25.3.1 SNPs in Candidate Genes
25.3.1.1 Inflammatory Cytokine Gene Polymorphisms
25.3.1.2 IL-1B
25.3.1.3 IL-17
25.3.1.4 IL-2
25.3.1.5 IL-8
25.3.1.6 TNF Family
25.3.1.7 HuGE Study
25.3.1.8 Toll-Like Receptors (TLRs)
25.3.1.9 Foxp3 Polymorphisms
25.3.2 Genes Involved in DNA Repair Mechanisms
25.3.2.1 Genes Involved in Metabolisation and Detoxification of Carcinogenic Compounds
25.3.2.2 Genes Involved in Tumour Suppression/Apoptosis
25.3.2.3 Genes Involved in Proliferation, Migration, Metabolism, Cell Differentiation, and Survival
25.3.2.4 DNA Methyltransferases (DNMTs)
25.3.2.5 Single Nucleotide Polymorphisms in microRNAs
25.3.2.6 GWAS
25.4 Clinical Implications of Genetic Polymorphisms
25.4.1 Association of Variants with Treatment Strategy
25.4.2 Association of Variants with Prognosis
25.4.3 Functional Investigation
25.5 Future Perspectives
25.6 Conclusions
Abbreviations
References
Index